Primary carnitine deficiency in two sisters with intractable epilepsy and reversible metabolic cardiomyopathy: Two case reports

Abstract

Primary carnitine deficiency (PCD) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. When carnitine cannot be transported into the cells, fatty acid oxidation is impaired, resulting a variety of symptoms, such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. The clinical manifestations and outcomes of different cases with PCD vary among patients. The present case report focused on two sisters with PCD. The younger sister presented with intractable epilepsy, and the older sister presented with reversible metabolic cardiomyopathy. Potential mutations in the SLC22A5 gene were investigated within the family, and a nonsense mutation [c.760C>T (p.R254X)] was identified in four family members. The two sisters harbored homozygous mutations, whereas their parents presented heterozygous mutations. Metabolic disease screening revealed low plasma free carnitine levels (<5 µmol/l) in the two sisters. The plasma free carnitine levels of their parents were normal, and they were asymptomatic. PCD in the two patients was managed using oral levocarnitine. The metabolic cardiomyopathy of the older sister improved following 3 months of treatment. However, the epilepsy of the younger sister was recurrent with oral antiepileptic therapy lasting one year and eight months, and epilepsy was finally controlled following right cerebral resection. The present case report demonstrated that the clinical manifestations presented by patients with PCD within the same family were different. The results indicated that treatment with levocarnitine supplementation should be initiated as soon as possible before irreversible organ damage occurs. In addition, metabolic decompensation and cardiac muscle functions were improved following carnitine supplementation. The resection of the severely diseased unilateral brain combined with carnitine supplementation and antiepileptic therapy may be an effective treatment for PCD with intractable epilepsy complications.

A report of a pedigree with compound heterozygous mutations in the SLC22A5 gene

“…Studies have shown that Carnitine deficiency was found in approximately 17% of patients with epilepsy (13). Yang et al (10) also reported a case of PCD with epilepsy. In the proband's older brother, the initial symptom was abdominal pain with an ongoing poor appetite and decreased endurance.…”

Dilated Cardiomyopathy (DCM) in an Infant Due to Primary Carnitine Deficiency (PCD); A Rare Case

“…which improved after carnitine supplementation [14]. Another study done by Xiyu-Fang Yang, showed the inability of the heart to maintain adequate circulation was improved after carnitine supplementation [15]. Perin F et al, in their study showed that a dilated cardiomyopathy cause due to carnitine deficiency was improved after oral supplementation with Lcarnitine [16].…”

Genetic landscape in Russian patients with familial left ventricular noncompaction

“…The SLC22A5 gene (also known as OCTN2 ) codes for the organic cation transporter novel 2 and is associated with the development of primary carnitine deficiency and cardiomyopathy ( 62 , 63 ). Here we present a family with the index patient diagnosed with LVNC and three family members diagnosed with DCM (see Supplementary Table S3 ).…”